Pulmonary and pleural localizations of Kaposi's sarcoma in AIDS

Intrathoracic Kaposi's sarcoma (KS) in AIDS is remarkable for its frequency and severity. It is responsible for 10% of "pneumonias" and almost 50% of pleurisies observed in these patients. The time elapsed between the discovery of the lesion and the patient's death does not exceed a few months on average. The initial manifestations of pulmonary KS are usually discreet and consist of cough and/or dyspnoea in patients with KS of the skin and mucosae. Fever is lacking or moderate. The most suggestive radiological findings are dense, nodular, tumour-like opacities and bilateral linear and/or micronodular opacities around the bronchi and vessels. The diagnosis rests on bronchial fibroscopy which shows red, non friable lesions which, to a trained endoscopist, are very characteristic. When these lesions are absent, thoracotomy may be necessary for diagnostic purposes. Treatment essentially consists of chemotherapy; zidovudine therapy and prophylaxis of pneumocystosis are indicated if the circulating CD 4 cell count falls below 200/mm3. When its symptoms are predominant, pleural KS is typically progressive, with normal or slightly elevated temperature, associated parenchymal lesions that are clearly visible on CT scans and copious, bilateral, blood-stained serous or chylous pleural fluid. When these signs are absent throacoscopy or thoracotomy may be necessary. Future advances in this field will be due not only to improvements in chemotherapy but also to a better understanding of the physiopathology of intrathoracic Kaposi's sarcoma.     

Acute biochemical variations induced by four different calcium salts in healthy male volunteers

Calcium (Ca) supplements have positive effects in growing children, reduce bone loss in late-postmenopausal women with a low calcium diet and, in association with vitamin D₃ supplements, may reduce non-vertebral fracture rates in elderly women. However, for many formulated pharmaceutical products their relative beneficial effects have not been conclusively established. We have compared the acute (6 h) metabolic responses following oral administration of two preparations of calcium gluconolactate and carbonate (CG and CG), tricalcium phosphate (TCP) and calcium citrate (CC), given on separate occasions in each of 10 healthy young male volunteers. The subjects fasted overnight for 12 h and continued to fast during the experimental procedure. A 1000 mg dose of each Ca salt was ingested at weekly intervals. Blood was drawn after 30, 60, 90, 120, 180, 240, 300 and 360 min for measurement of serum Ca, phosphorus (P), parathyroid hormone (PTH) and whole plasma calcitonin (iCT). All Ca supplements induced significant (+6.4% to +8.1%;p<0.01) increases in Ca and significant suppression of PTH (–37.4% to –57.4%;p<0.01). Comparison of response curves revealed significantly (p<0.01) more marked Ca increase and PTH suppression with CC than with the other three Ca salts. CG' and CC induced marginal decreases in serum P and the overall curve of P variations was different for TCP compared with CG, CG and CC. No significant variation of iCT was recorded during the test. We conclude that all four Ca supplements seem to be absorbed to some extent since they induce significant biochemical variations that may lead to a reduction in bone turnover and that CC induces a significantly larger increase in serum Ca and a significantly greater suppression of serum PTH.     

The Pichia pastoris HIS4 gene: nucleotide sequence,creation of a non-reverting his4 deletion mutant,and development of HIS4-based replicating and integrating plasmids

We have obtained a clone of the Pichia pastoris HIS4 gene and have determined its nucleotide sequence. Based upon its deduced amino-acid sequence, the product of the P. pastoris HIS4 gene has the same structural organization as the Saccharomyces cerevisiae His4 protein and appears to encode a trifunctional enzyme catalyzing the second (phosphoribosyl-ATP pyrophosphohydrolase), third (phosphoribosyl-AMP cyclohydrolase), and tenth (histidinol dehydrogenase) steps in histidine biosynthesis. The chromosomal copy of the HIS4 gene was disrupted by homologous recombination, creating the strain SGY58. The his4 deletion mutation in this strain lacks the entire coding region of this gene and has a reversion rate that is undetectable. A set of complementary plasmids that carry the HIS4 gene was also developed. Among these are nine E. coli-P. pastoris shuttle vectors that transform the His4 deletion mutant at high efficiency and an integration vector for creating site-specific alterations of the P. pastoris genome.     

Effect of Perfusate pH on Reduction of Quinidine Capillary Permeability by Albumin in Isolated Perfused Rat Heart

It has been suggested that albumin reduces quinidine capillary permeability (PS) in the single-pass perfused heart preparation by reducing paracellular transport of quinidine ions. Using this preparation, we examined the effect of albumin (0.1 per cent) on quinidine PS at perfusate pHs of 7.1 and 7.9 during uptake of quinidine (19 µM) and also during washout of the drug using a randomized design. Quinidine PS was approximately 16 ml/min/g heart at pH 7.9 and was not altered by the presence of albumin in perfusate. At pH 7.1, in the absence of albumin, quinidine PS was also 16 ml/min/g, but in the presence of albumin (0.1 per cent) PS was reduced significantly to approximately 5 ml/min/g (P < 0.001). In the absence of albumin PS was the same at pH 7.1 and 7.9 in spite of a greater degree of ionisation of quinidine at pH 7.1. This suggests that there is significant uptake of ionised quinidine at pH 7.1. The greater effect of albumin on PS at pH 7.1 supports the hypothesis that albumin reduces paracellular transport of quinidine ions.     

Acute Toxicity, Toxicokinetics, and Tissue Target of Lead and Uranium in the Clam Corbicula fluminea and the Worm Eisenia fetida: Comparison with the Fish Brachydanio rerio

The general objective of our work was to propose new reference material for chemical toxicity testing and new sentinel organisms for environmental quality survey programs (freshwater or soils). We also wanted to provide basic toxicological data on the environmental effects of uranium. Thus, we conducted a comparative study to establish the acute toxicity and toxicokinetics of lead (Pb) and uranium (U) to the bivalve mollusc Corbicula fluminea and the terrestrial annelid Eisenia fetida andrei and to compare these findings with those of the well-known teleost fish Brachydanio rerio. We then measured the concentration of these metals in various tissues of the clam and the worm after two periods of exposure (4 and 11 days) to identify the affinities of these tissues for Pb and U. Our results have shown that Pb and U are very toxic to Eisenia and relatively nontoxic to Corbicula. By comparison, Pb was relatively nontoxic and U appeared to be very toxic to the fish. The toxicokinetic studies indicated that the three species are able to accumulate Pb and U, the rate and level of accumulation depending both on the species and the metal. We also found that fish and clams depurate the two metals. Data collected for the worm were conflicting: Pb was not depurated whereas tissue concentrations of U declined after the eighth day of exposure. Our study has also shown that the tissue distribution of Pb in the mollusc and in the earthworm differs significantly from that of U, both after 4 and 11 days exposure. In conclusion, these three species showed potential as bioindicators of environmental contamination by metals. Indeed, they could be used in conjunction to test different compartments of an ecosystem: worms for soils, fish for the water column, and clams for the water/sediment interface. Received: 30 October 1996/Accepted: 1 September 1998     

Ginkgo biloba extract EGb761 reduces the development of amphetamine-induced behavioral sensitization: effects on hippocampal type II corticosteroid receptors

Pretreatment of rats with the extract of Ginkgo biloba termed EGb761 reduced the behavioral sensitization induced by successive -amphetamine administrations (0.5 mg/kg) as estimated by increasing values of locomotor activity. EGb761 pretreatment also prevented the reduced density of [³H]dexamethasone binding sites in the dentate gyrus and the CA1 hippocampal regions of -amphetamine treated animals. These observations suggest that EGb761, by reducing glucocorticoid levels, could modulate the activity of the neuronal systems involved in the expression of the behavioral sensitization.     

Dose related response to clozapine in a state psychiatric hospital population: A naturalistic study

After noting a striking difference in the dosing practices of two treating psychiatrists, each responsible for the operation of a clozapine unit in a state psychiatric hospital, the authors conducted a retrospective chart review to assess the clinical efficacy of low dose mg. per day) versus high dose ( mg. per day) clozapine treatment for a cohort of 31 inpatients. Levels of psychopathology, behavior, and social functioning were assessed six months pre and during clozapine treatment for 16 patients who received low dose clozapine treatment and 15 patients who received high dose clozapine treatment. Patients on both units demonstrated significant reductions in their levels of psychopathology, improved social functioning and improvement in their behavior following six months clozapine treatment. This naturalistic study suggests that the use of low dose clozapine provides effective treatment for chronic, severely treatment resistant inpatients with schizophrenia or schizo-affective illness, at the same time reducing the potential for significant side effects.     

Inducible nitric oxide synthase activity of cloned murine microglial cells

Nitric oxide (NO) is a short-lived diffusable molecule now believed to participate in multiple physiologic functions in the CNS including neurotransmission and the maintenance of vascular tone. Previously, we reported that cell lines obtained by retroviral immortalization of tissue macrophages (M?;) could be induced to synthesize nitrite (NO), a stable end product of the NO synthetic pathway. We have further characterized the induction and activity of this pathway in a panel of seven microglial clones derived from primary embryonic mouse brain cultures. Like M?;, these clones were found to release high levels of NO_-² in response to recombinant interferon-γ (rIFN-γ) as a priming signal together with either bacterial lipopolysaccharide (LPS) or exogenous recombinant tumor necrosis factor-α (rTNF-α). As previously demonstrated for M?;, phagocytosis of zymosan particles during induction of enzyme activity enhanced subsequent NO production, which is of interest in light of the postulated phagocytic role of microglia within the CNS. Biochemical characterization of enzyme activity in intact microglial clones and in isolated cytosolic fractions indicates that the microglial NO synthase present in these murine cell clones represents the M?;-like isotype. These findings suggest that microglial cells could represent a major source of NO within the CNS.